Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001295498 | SCV001484423 | uncertain significance | Hypertrophic cardiomyopathy | 2022-09-02 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 42530). This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 27532257). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 474 of the MYBPC3 protein (p.Glu474Asp). |
Color Diagnostics, |
RCV001804756 | SCV002053591 | uncertain significance | Cardiomyopathy | 2023-10-26 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with aspartic acid at codon 474 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with dilated cardiomyopathy (PMID: 22464770, 24503780, 27532257). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Laboratory for Molecular Medicine, |
RCV000035396 | SCV000059044 | uncertain significance | not specified | 2009-07-21 | no assertion criteria provided | clinical testing |